Circulating biomarkers play a critical role in the diagnosis and management of patients with chronic heart failure (Braunwald, N. Engl. J. Med. 358:2148-2159, 2008). Natriuretic peptides, such as brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), have been demonstrated to be powerful tools for the diagnosis, risk stratification, and management of patients with heart failure (Felker et al., Canadian Med. Assoc. J. 175:611-617, 2006). In addition to being useful for clinical management, biomarkers can provide insights into the mechanisms underlying important physiologic relationships. Exercise intolerance, typically manifested as exertional dyspnea, is a major morbidity of chronic heart failure. Both maximal (e.g., as measured by peak oxygen uptake [peak VO2]) (Aaronson et al., Circulation 95:2660-2667, 1997; Mancini et al., Circulation 83:778-786, 1991) and submaximal exercise capacity (e.g., as measured by distance in the 6-minute walk test) (Bittner et al., JAMA 270:1702-1707, 1993) have been demonstrated to be of substantial prognostic importance in chronic heart failure.
A variety of therapies can be used to treat patients diagnosed with a cardiovascular disease. For example, exercise therapy is commonly used to treat patients diagnosed with a cardiovascular disease (see, for example, Korhonen et al., J. Womens Health 20:1051-1064, 2011).